Background: A body of evidence is accumulating suggesting a role for statins in endothelial function, including anti-inflammatory and proangiogenic activities. To address this issue, we investigated the gene expression patterns induced by rosuvastatin in vitro in endothelial cells and in vivo in apoE-/- mice. Methods and Results: In human endothelial cells (HUVECs and HAEC) treatment with rosuvastatin 10μM induced eNOS, VEGF and KDR expression relative to cell under control conditions. For in vivo studies, 20 apoE-/- mice were fed with a cholesterol rich diet, plus rosuvastatin 10 mg/kg/day, and 10 mice with only the cholesterol rich diet. Rosuvastatin treatment reduced plasma levels of total cholesterol (TC) and triglycerides (TG) by 42% and by 22% respectively (p<0.05). The lesion area in the ascending aorta was reduced by 50.3% in animals treated with rosuvastatin (19725±7860μm2 vs 39697±18712μm2 p=0.06). Collagen deposition was reduced at the ascending aorta level (22.76±6.3% vs 36.58±13.1% p<0.05). mRNA levels for a-actin in the vascular wall were reduced while no difference was observed in the expression of CD68, CD4, IL6, IL10, MCP-1, eNOS, VEGF and TF. Summary: in vitro rosuvastatin treatment resulted in eNOS, KDR and VEGF mRNA induction both in HUVECS and HAEC cells. In vivo rosuvastatin treatment in Apo E KO mice fed a cholesterol rich diet resulted in decreased atherosclerosis mainly at the ascending aorta, paralleled by a decreased expression of markers for smooth muscle cells, while no changes in macrophages and T-lymphocytes were observed
Effects of rosuvastatin on endothelial and vascular wall gene expression / G.D. Norata, P. Marchesi, K. Garlaschelli, A.L. Catapano. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 8:1(2007 Jun), pp. 200-200. (Intervento presentato al 76. convegno EAS Congress tenutosi a Helsinki nel 2007) [10.1016/S1567-5688(07)71761-0].
Effects of rosuvastatin on endothelial and vascular wall gene expression
G.D. NorataPrimo
;P. MarchesiSecondo
;K. GarlaschelliPenultimo
;A.L. CatapanoUltimo
2007
Abstract
Background: A body of evidence is accumulating suggesting a role for statins in endothelial function, including anti-inflammatory and proangiogenic activities. To address this issue, we investigated the gene expression patterns induced by rosuvastatin in vitro in endothelial cells and in vivo in apoE-/- mice. Methods and Results: In human endothelial cells (HUVECs and HAEC) treatment with rosuvastatin 10μM induced eNOS, VEGF and KDR expression relative to cell under control conditions. For in vivo studies, 20 apoE-/- mice were fed with a cholesterol rich diet, plus rosuvastatin 10 mg/kg/day, and 10 mice with only the cholesterol rich diet. Rosuvastatin treatment reduced plasma levels of total cholesterol (TC) and triglycerides (TG) by 42% and by 22% respectively (p<0.05). The lesion area in the ascending aorta was reduced by 50.3% in animals treated with rosuvastatin (19725±7860μm2 vs 39697±18712μm2 p=0.06). Collagen deposition was reduced at the ascending aorta level (22.76±6.3% vs 36.58±13.1% p<0.05). mRNA levels for a-actin in the vascular wall were reduced while no difference was observed in the expression of CD68, CD4, IL6, IL10, MCP-1, eNOS, VEGF and TF. Summary: in vitro rosuvastatin treatment resulted in eNOS, KDR and VEGF mRNA induction both in HUVECS and HAEC cells. In vivo rosuvastatin treatment in Apo E KO mice fed a cholesterol rich diet resulted in decreased atherosclerosis mainly at the ascending aorta, paralleled by a decreased expression of markers for smooth muscle cells, while no changes in macrophages and T-lymphocytes were observedPubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.